Nosocomial infections with antibiotic-resistant bacteria increase the cost of health care, length of hospital stay and mortality. The incidence of antibiotic-resistant bacteria such as imipenem-resistant Pseudomonas aeruginosa is increasing. Present-day infection control measures have failed to curb the increasing incidence of antibiotic-resistant bacteria. Few new antibiotics that target resistant gram-negative bacteria are under development. All these reasons underscore the need to better understand the causal risk factors of prototypical antibiotic-resistant bacteria such as imipenem-resistant Pseudomonas that will lead to cost-effective prospective interventions. No previous study of the magnitude proposed in this grant (5-year cohort) or with the clinical and molecular epidemiologic rigor proposed below has been done to assess the causality and interaction of the following risk factors for imipenem-resistant Pseudomonas: antibiotic exposure, patient-to-patient transmission,and being colonized with a previously susceptible identical species strain. Specific aims are: Aim 1: Determine the association between prior treatment with imipenem and other anti-pseudomonal antibiotics and the outcome of acquisition of imipenem-resistant Pseudomonas. Aim 2: Use molecular techniques (MLST and PFGE) to quantify the percent of acquisition of imipenem-resistant P. aeruginosa that is due to patient-to-patient transmission. [unreadable] Aim 3: In the subset of patients who are initially colonized with imipenem-susceptible Pseudomonas aeruginosa and subsequently found to carry an imipenem-resistant strain, we will use MLST and PFGE to assess the genetic relatedness in a given patient between the imipenem-susceptible Pseudomonas and imipenem-resistant Pseudomonas aeruginosa isolate and determine the mechanism of resistance. [unreadable] Aim 4: Determine the cost-effectiveness of three different infection control interventions. [unreadable] [unreadable] [unreadable]